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Pathogenetic and therapeutic approaches to IgA nephropathy using a spontaneous animal model, the ddY mouse

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Abstract

IgA nephropathy is the most common primary chronic glomerulonephritis in the world and was first described by Berger et al. (J Urol Nephrol 74:694–695;1968). Histopathologically, IgA nephropathy is characterized by expansion of the glomerular mesangial matrix with mesangial cell proliferation. Glomeruli typically contain generalized diffuse granular mesangial deposits of IgA (mainly IgA1), IgG and C3. In advanced patients, global glomerular sclerosis, crescent formation and tubulo-interstitial fibrosis are marked in light microscopy. IgA nephropathy is generally considered to be an immune-complex mediated glomerulonephritis. Although more than 40 years have passed since this disease was firstly described, the pathogenesis/initiation factors of IgA nephropathy are still obscure. The objective of this review is to explain the pathogenesis and treatment based on our previous data of ddY mouse, a spontaneous animal model for IgA nephropathy.

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References

  1. Berger J, Hinglais N. Les Depots intercapillaries d’IgA-IgG. J Urol Nephrol. 1968;74:694–5.

    CAS  Google Scholar 

  2. Koyama A, Igarashi M, Kobayshi M. Natural history and risk factors for immunoglobulin A nephropathy in Japan. Research Group on Progressive Renal Diseases. Am J Kidney Dis. 1997;29:526–32.

    Article  CAS  PubMed  Google Scholar 

  3. Maeda A, Gohda T, Funabiki K, Horikoshi S, Shirato I, Tomino Y, et al. Significance of serum IgA levels and serum IgA/C3 ratio in diagnostic analysis of patients with IgA nephropathy. J Clin Lab Anal. 2003;17:73–6.

    Article  CAS  PubMed  Google Scholar 

  4. Nakayama K, Ohsawa I, Maeda-Ohtani A, Murakoshi M, Satoshi Horikoshi S, Tomino Y. Prediction of diagnosis of immunoglobulin A nephropathy prior to renal biopsy and correlation with urinary sediment findings and prognostic grading. J Clin Lab Anal. 2008;22:114–8.

    Article  CAS  PubMed  Google Scholar 

  5. Okazaki K, Suzuki Y, Kobayashi T, Kodama F, Horikoshi S, Tomino Y. Influence of the period onset to medical intervention on renal prognosis in IgA nephropathy (in preparation).

  6. Tomino Y. IgA nephropathy: lessons from an animal model, the ddY mouse. J Nephrol. 2008;21:464–7.

    Google Scholar 

  7. Tomino Y. Lessons from the spontaneous mouse model for treatment of type 2 diabetic nephropathy and IgA nephropathy. Juntendo Med J. 2009;55:223–34.

    Google Scholar 

  8. Imai H, Nakamoto Y, Asakura K, Miki K, Yasuda T, Miura AB, et al. Spontaneous glomerular IgA deposition in ddY mice: an animal model of IgA nephritis. Kidney Int. 1985;27:756–61.

    Article  CAS  PubMed  Google Scholar 

  9. Muso E, Yoshida H, Takeuchi E, Shimada T, Yashiro M, Sugiyama T, et al. Pathogenic role of polyclonal and polymeric IgA in a murine model of meangial proliferative glomerulonephritis with IgA deposition. Clin Exp Immunol. 1991;84:459–65.

    CAS  PubMed  Google Scholar 

  10. Miyawaki S, Muso E, Takeuchi E, Matsushima H, Shibata Y, Sasayama S, et al. Selective breeding for high serum IgA levels from noninbred ddY mice: Isolation of a strain with an early onset of glomerular IgA deposition. Nephron. 1997;76:201–7.

    Article  CAS  PubMed  Google Scholar 

  11. Suzuki H, Suzuki Y, Yamanaka T, Hirose S, Nishimura H, Toei J, et al. Genome-wide scan in a novel IgA nephropathy model identifies a susceptibility locus on murine chromosome 10, in a region synthenic to human IGAN1on chromosome 6Q22–23. J Am Soc Nephrol. 2005;16:1289–99.

    Article  CAS  PubMed  Google Scholar 

  12. Gharavi AG, Yan Y, Scolari F, Schena FP, Frasca GM, Ghiggeri GM, et al. IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6Q22-23. Nat Genet. 2000;26:354–7.

    Article  CAS  PubMed  Google Scholar 

  13. Takeuchi E, Doi T, Shimada T, Muso E, Maruyama N, Yoshida H, et al. Retroviral gp70 antigen in spontaneous mesangial glomerulonephritis of ddY mice. Kidney Int. 1989;35:638–46.

    Article  CAS  PubMed  Google Scholar 

  14. Shimizu M, Tomino Y, Abe M, Shirai T, Koide H. Retroviral envelope glycoprotein (gp70) is not a prerequisite for pathogenesis of primary immunoglobulin A nephropathy in ddY mice. Nephron. 1992;62:328–31.

    Article  CAS  PubMed  Google Scholar 

  15. Suzuki H, Suzuki Y, Narita I, Aizawa M, Kihara M, Yamanaka T, et al. Toll-like receptor 9 affects severity of IgA nephropathy. J Am Soc Nephrol. 2008;19:2384–95.

    Article  CAS  PubMed  Google Scholar 

  16. Roos A, Rastaldi MP, Calvaresi N, Oortwijn BD, Schlagwein N, van Gijlswijk-Janssen DJ, et al. Glomerular activation of the lectin pathway of complement in IgA nephropathy is associated with more severe renal disease. J Am Soc Nephrol. 2006;17:1724–34.

    Article  CAS  PubMed  Google Scholar 

  17. Onda K, Ohi H, Tamano M, Ohsawa I, Wakabayashi M, Horikoshi S, et al. Hypercomplementemia in adult patients with IgA nephropathy. J Clin Lab Anal. 2007;21:77–84.

    Article  CAS  PubMed  Google Scholar 

  18. Lemley KV, Lafayette RA, Safai M, Derby G, Blouch K, Squarer A, et al. Podocytopenia and disease severity in IgA nephropathy. Kidney Int. 2002;61:1475–85.

    Article  PubMed  Google Scholar 

  19. Kriz W, Kretzler M, Nagata M, Provoost AP, Shirato I, Uiker S, et al. A frequent pathway to glomerulosclerosis: Detection of tuft architecture-podocyte damage-segmental sclerosis. Kidney Blood Press Res. 1996;18:245–53.

    Article  Google Scholar 

  20. Hishiki T, Shirato I, Takahashi Y, Funabiki K, Horikoshi S, Tomino Y. Podocyte injury predicts progonosis in patients with IgA nephropathy using a small amount of renal biopsy tissue. Kidney Blood Press Res. 2001;24:99–104.

    Article  CAS  PubMed  Google Scholar 

  21. Hara M, Yanagihara T, Kihara I, Higashi K, Fujimoto K, Kajita T, et al. Apical cell membrane are shed into urine from injured podocytes: A novel phenomenon of podocyte injury. J Am Soc Nephrol. 2005;16:408–16.

    Article  CAS  PubMed  Google Scholar 

  22. Church MK, Levi-Schaffer F. The human mast cell. J Allergy Clin Immunol. 1997;99:155–60.

    Article  CAS  PubMed  Google Scholar 

  23. Liao J, Hayashi K, Horikoshi S, Ushijima H, Kimura J, Tomino Y, et al. Effects of steroid-liposome on immunohistopathology of IgA nephropathy in ddY mice. Nephron. 2001;89:194–200.

    Article  CAS  PubMed  Google Scholar 

  24. Iwata Y, Wada T, Uchiyama A, Miwa A, Nakaya I, Tohyama T, et al. Remission of IgA nephropathy after allogenic peripheral blood stem cell transplantation followed by immunosuppression for acute lymphocytic leukemia. Intern Med. 2006;45:1291–5.

    Article  PubMed  Google Scholar 

  25. Imasawa T, Nagasawa R, Utsunomiya Y, Kawamura T, Zhong Y, Makita N, et al. Bone marrow transplantation attenuates murine IgA nephropathy: role of a stem cell disorder. Kidney Int. 1999;56:1809–17.

    Article  CAS  PubMed  Google Scholar 

  26. Suzuki H, Suzuki Y, Aizawa M, Yamanaka T, Kihara M, Pang H, et al. Th1 polarization in murine IgA nephropathy directed by bone-marrow-derived cells. Kidney Int. 2007;72:319–27.

    Article  CAS  PubMed  Google Scholar 

  27. Ohmuro H, Shimizu M, Tsushima Y, Kodera S, Kuramoto T, Fukui M, et al. Effect of low-protein diet on glomerular changes in ddY mice: a spontaneous animal model of IgA nephropathy. Nephron. 1996;72:333–4.

    Google Scholar 

  28. Tomino Y. Long term effects of dilazep hydrochloride, an anti-platelet drug, on patients with IgA nephropathy-Reports of 5-year treatment. Curr Top Pharmacol 2007;11:45–9.

    Google Scholar 

  29. Suzuki Y, Thang NT, Horikoshi S, Shirato I, Nakamura S, Kimura M, et al. Effect of Valsartan, an angiotensin II AT1 receptor blocker, on the glomerular fibrosis of IgA nephropathy in ddY mice. Nephron. 2000;86:374–5.

    Google Scholar 

  30. Shimizu M, Shou I, Tsuge T, Abe M, Tomino Y. Effect of mizoribine on glomerulonephritis of early-stage IgA nephropathy in ddY mice. Nephron. 1998;79:67–72.

    Google Scholar 

  31. Tomino Y, Shimizu M, Koide H, Abe M, Shirai T. Effect of monoclonal antibody CD4 on glomerulonephritis of ddY mice, a spontaneous animal model of IgA nephropathy. Am J Kidney Dis. 1993;21:427–32.

    Google Scholar 

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Acknowledgments

I sincerely thank my colleagues in the Division of Nephrology, Department of Internal Medicine at Juntendo University Faculty of Medicine, Tokyo, Japan.

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Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Yasuhiko Tomino

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  1. Yasuhiko Tomino
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Correspondence to Yasuhiko Tomino.

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Presented at the 53rd Annual Meeting of the Japanese Society of Nephrology.

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Tomino, Y. Pathogenetic and therapeutic approaches to IgA nephropathy using a spontaneous animal model, the ddY mouse. Clin Exp Nephrol 15, 1–7 (2011). https://doi.org/10.1007/s10157-010-0359-z

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